Impaired neuromuscular transmission of the tibialis anterior in a rodent model of hypertonia

Matthew J. Fogarty, Gary C. Sieck, Joline E. Brandenburg

Research output: Contribution to journalArticle

Abstract

Early-onset hypertonia is characteristic of developmental neuromotor disorders, including cerebral palsy (CP). The spa transgenic mouse displays early-onset spasticity, abnormal gait, and motor impairments that are remarkably similar to symptoms of human CP. Previously, we showed that spa mice have fewer motor neurons innervating the tibialis anterior (TA). An expanded innervation ratio may result in increased susceptibility to neuromuscular transmission failure (NMTF). We assessed NMTF in an ex vivo TA muscle nerve preparation from spa and wild-type (WT) mice by comparing forces elicited by nerve versus muscle stimulation. TA muscle innervation ratio was assessed by counting the number of muscle fibers and dividing by the number of TA motor neurons. Muscle fiber cross-sectional areas were also assessed in the TA muscle. We observed that NMTF was immediately present in spa mice, increased with repetitive stimulation, and associated with increased innervation ratio. These changes were concomitant with reduced TA muscle fiber cross-sectional area in spa mice compared with WT. Early-onset hypertonia is associated with increased innervation ratio and impaired neuromuscular transmission. These disturbances may exacerbate the underlying gait abnormalities present in individuals with hypertonia. NEW & NOTEWORTHY Nerve-muscle interaction is poorly understood in the context of early-onset spasticity and hypertonia. In an animal model of early-onset spasticity, spa mice, we found a marked impairment of tibialis anterior neuromuscular transmission. This impairment is associated with an increased innervation ratio (mean number of muscle fibers innervated by a single motor neuron). These disturbances may underlie weakness and gait disturbances observed in individual with developmental hypertonia and spasticity.

Original languageEnglish (US)
Pages (from-to)1869-2020
Number of pages152
JournalJournal of neurophysiology
Volume123
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Innervation ratio
  • Muscle fibers
  • Neuromotor
  • Spastic cerebral palsy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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